Basic Biology for CS262OverviewBioinformatics schematic of a cellWatson and CrickNucleic acids (DNA and RNA)NucleotidesSlide 7PowerPoint PresentationProteinsSlide 10DipeptideProtein structureDNA in actionThe need for an intermediarySlide 15Slide 16The IntermediaryNext question…The Genetic CodeSlide 20TranslationtRNASlide 23The gene and the genomeMore complexitySplicingCentral Dogma of Molecular BiologyCentral dogmaTranscription – key stepsSlide 30Slide 31PromotersGenes can be switched on and offRegulation of genesRegulatory sequencesSlide 36AcknowledgmentsBasic Biology for CS262OMKAR DESHPANDE (TA)OverviewStructures of biomoleculesHow does DNA function?What is a gene?How are genes regulated?Bioinformatics schematic of a cellWatson and CrickNucleic acids (DNA and RNA)Form the genetic material of all living organisms.Found mainly in the nucleus of a cell (hence “nucleic”)Contain phosphoric acid as a component (hence “acid”)They are made up of nucleotides.NucleotidesA nucleotide has 3 componentsSugar (ribose in RNA, deoxyribose in DNA)Phosphoric acidNitrogen base Adenine (A)Guanine (G)Cytosine (C)Thymine (T) or Uracil (U)NucleotidesPhosphate GroupSugarNitrogenousBasePhosphate GroupSugarNitrogenousBaseTCACTGGCGAGTCAGCGAGUCAGCDNA RNAA = TG = CT UComposed of a chain of amino acids. R | H2N--C--COOH | HProteins20 possible groupsR R | | H2N--C--COOH H2N--C--COOH | | H H ProteinsDipeptide R O R | II | H2N--C--C--NH--C--COOH | | H H This is a peptide bondProtein structureLinear sequence of amino acids folds to form a complex 3-D structure.The structure of a protein is intimately connected to its function.DNA in actionQuestions about DNA as the carrier of genetic information:How is the information stored in DNA?How is the stored information used ?Answers:Information is stored as nucleotide sequences... and used in protein synthesis.The need for an intermediaryFact 1 : Ribosomes are the sites of protein synthesis.Fact 2 : Ribosomes are found in the cytoplasm.The need for an intermediaryThe need for an intermediaryFact 1 : Ribosomes are the sites of protein synthesis.Fact 2 : Ribosomes are found in the cytoplasm.Question : How does information ‘flow’ from DNA to protein?The IntermediaryRibonucleic acid (RNA) is the “messenger”.The “messenger RNA” (mRNA) can be synthesized on a DNA template.Information is copied (transcribed) from one strand of DNA to mRNA. (TRANSCRIPTION)Next question…How do I interpret the information carried by mRNA?Think of the sequence as a sequence of “triplets”.Think of AUGCCGGGAGUAUAG as AUG-CCG-GGA-GUA-UAG.Each triplet (codon) maps to an amino acid.The Genetic Codef : codon amino acid1968 Nobel Prize in medicine – Nirenberg and KhoranaImportant – The genetic code is universal!It is also redundant / degenerate.The Genetic CodeTranslationThe sequence of codons is translated to a sequence of amino acids.Transfer RNA (tRNA) – a different type of RNA – matches amino acids to codons in mRNA.Freely float in the cytoplasm.Every amino acid has its own type of tRNA that binds to it alone.Anti-codon – codon binding crucial.Show animationtRNAtRNAThe gene and the genomeA sequence of nucleotides on the DNA that encodes a polypeptide is called a gene.Genome = Set of all genes in the organism + junk stuff (the entire DNA content).More complexityThe RNA message is sometimes “edited”.Exons are nucleotide segments whose codons will be expressed.Introns are intervening segments (genetic gibberish) that are snipped out.Exons are spliced together to form mRNA.SplicingfrgjjthissentencehjfmkcontainsjunkelmthissentencecontainsjunkCentral Dogma of Molecular BiologyDNA RNA Protein Phenotype Transcription : DNA RNATranslation : RNA ProteinCentral dogmaDNAtRNArRNAsnRNAmRNAtranscriptiontranslationPOLYPEPTIDEZOOM INTranscription – key stepsInitiationElongationTerminationDNATranscription – key stepsInitiationElongationTerminationDNATranscription – key stepsInitiationElongationTermination+DNARNADNAPromotersPromoters are sequences in the DNA just upstream of transcripts that define the sites of initiation.The role of the promoter is to attract RNA polymerase to the correct start site so transcription can be initiated.5’Promoter3’Genes can be switched on and offIn an adult multicellular organism, there is a wide variety of cell types seen in the adult. eg, muscle, nerve and blood cells.The different cell types contain the same DNA though.This differentiation arises because different cell types express different genes.Regulation of genesWhat turns genes on and off?When is a gene turned on or off?Where (in which cells) is a gene turned on?How many copies of the gene product are produced?Regulatory sequencesThese are binding sites for proteins, often short stretches of DNA (~25 nucleotides).Inexactly repeating patterns (“motifs”).Motifs stand out as highly conserved regions in a multiple sequence alignment.Regulatory sequencesAcknowledgmentsMartin Tompa, for a couple of slides on gene regulation vector.cshl.org/dnaftb/ for the tRNA figures, and the protein synthesis animationRuss Altmann, for the figure on “Bioinformatics Schematic of a
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